Physiological pH Environment Research Articles

Lighting Up Nucleolus To Report Mitochondria Damage Using a Mitochondria-to-Nucleolus Migration Probe.

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

Non-enzymatic Glucose Detection by Fe2O3 Nanorods-reduced Graphene under Physiological pH

Background: Non-enzymatic detection has become a research hotspot because of its alternativity in solving problems compared to enzymatic biosensors, but most of those sensors require a strong basic pH environment (higher than 10) to active their surface, restricting their use in clinical detection because the pH of body fluid is around 7.4. Furthermore, metal oxide sensors with specific morphologies are reported to have a fast electrocatalytic response. Therefore, Fe2O3 nanocomposites with porous structure are selected for glucose detection research in a physiological pH environment. Objective: The study aimed to assess the potential use of porous reduced graphene oxide-Fe2O3 nanorods in glucose detection in a physiological pH environment. Method: Hydrothermal method was used to prepare porous Fe2O3-rGO NRs (Nanorods) and hollow Fe2O3/C nanoparticles. Cyclic voltammetry and electrochemical impedance spectroscopy were used to evaluate the performance of our materials. Results: Porous-reduced graphene oxide-Fe2O3 nanorods have exhibited better performance than hollow carbon-Fe2O3 core-shell nanoparticles for glucose detection in a physiological pH environment. Conclusion: Non-enzymatic glucose sensing based upon cavity Fe2O3-rGO NRs under a physiological pH environment has been successfully realized, attributing to their high electron mobility and large specific surface area. Furthermore, the results of this work indicate that the glucose sensor prepared here has shown good repeatability and stability, which suggests its potential use in clinical detection.

Modifying Fluorescent Protein Chromophore to Detect Protamine and Application in Real Serum Samples

AbstractAs effective methods to accurately and rapidly detect protamine remains a major challenge, here we present a fluorescent protein chromophore‐based probe (IDL‐FP) utilizing twisted‐intramolecular charge transfer (TICT) to detect protamine. The introduction of an electron‐donor group 4‐dimethylaminobenzaldehyde extends the emission wavelength of IDL‐FP to the red region. The deprotection of t‐butyloxy carbonyl groups can then generate an electronegative carboxyl group, which promotes the binding to protamine via electrostatic attraction. Thus, IDL‐FP is sensitive and specific towards protamine and can serve as a highly selective detector for protamine with a detection limit as low as 8.87 ng/mL. As IDL‐FP exhibited good stability in physiological pH environment, we successfully apply IDL‐FP to detect spiked‐in protamine in human serum. In summary, probe IDL‐FP is a promising tool for the quantitative determination of protamine.

Two thiazole-fused fluoran-based fluorescent probes for selective and sensitive sensing copper ions and cell imaging application

In this work, two thiazole-fused fluoran-based fluorescent probes 8′-(diethylamino)-2-((2-hydroxyethyl) amino)spiro[isoindoline-1,11′-xantheno[2, 1-d]thiazol]-3-one (TFH) and (8′-(diethylamino)-2-((2-hydroxyethyl)amino)-3′-methyl-3-oxospiro[isoindoline-1,11′-xantheno[2,1-d]thiazol]-3′-ium).BF4 (MTFH) have been prepared for copper ions. It should be noted that MTFH achieves red emission (632 nm) compared with TFH in the presence of copper ion, which mainly can be attributed to the methylation of molecule MTFH that induced more stronger ICT effect. The two probes show selective fluorescence off-on signal changes towards copper ions with detection limits of 8.8 and 60.8 nM. Copper ion detection can be conducted in a wide pH range including the physiological pH environment. Both TFH and MTFH exhibit suitable cytotoxicity and have been used for copper ion tracing in living cells. However, no other significant improvements of MTFH in sensing performance can be observed when compared with TFH.

Characterization and application of photocrosslinkable collagen maleate as bioink in extrusion-based 3D bioprinting.

3D bioprinting, a significant advancement in biofabrication, is renowned for its precision in creating tissue constructs. Collagen, despite being a gold standard biomaterial, faces challenges in bioink formulations due to its unique physicochemical properties. This study introduces a novel, neutral-soluble, photocrosslinkable collagen maleate (ColME) that is ideal for 3D bioprinting. ColME was synthesized by chemically modifying bovine type I collagen with maleic anhydride, achieving a high substitution ratio that shifted the isoelectric point to enhance solubility in physiological pH environments. This modification was confirmed to preserve the collagen's triple-helix structure substantially. Bioprinting parameters for ColME were optimized, focusing on adjustments to the bioink concentration, extrusion pressure, nozzle speed, and temperature. Results demonstrated that lower temperatures and smaller nozzle sizes substantially improved the print quality of grid structures. Additionally, the application of intermittent photo-crosslinking facilitated the development of structurally robust 3D multilayered constructs, enabling the stable fabrication of complex tissues. Cell viability assays showed that encapsulated cells within the ColME matrix maintained high viability after printing. When compared to methacrylated gelatin, ColME exhibited superior mechanical strength, resistance to enzymatic digestion, and overall printability, positioning it as an outstanding bioink for the creation of durable, bioactive 3D tissues.

Contributions of Cathepsin A and Carboxylesterase 1 to the hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis

The prodrug tenofovir alafenamide (TAF) is a first‐line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitroincubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH‐dependent manner. At their physiological pH environment, the activity of CatA (pH 5.2) was 700‐1000‐fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200‐fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis‐(p‐nitrophenyl) phosphate. Moreover, an in vitrostudy revealed that the CES1 variant G143E (rs71647871) is a loss‐of‐function variant for CES1‐mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation.

Acidic microenvironment triggered in situ assembly of activatable three-arm aptamer nanoclaw for contrast-enhanced imaging and tumor growth inhibition in vivo.

Rationale: Static assembled multivalent DNA nanotheranostics system have encountered some bottleneck problems in cancer imaging and therapy, such as poor penetration and high immunogenicity. Herein, we proposed an acidic tumor microenvironment triggered assembly of activatable multivalent nanodevice, called “three-arm aptamer nanoclaw” (TA-aptNC), assembled from three pH-responsive aptamer-decorated DNA monomers (pH-aptDMs) to facilitate their functions of imaging and therapy.Methods: The activated TA-aptNC was constructed by acidic microenvironment triggered in situ assembly of three pH-aptDMs. Designer pH-aptDM was established based on the combination of a pH-responsive i-motif switch and an assembly module with a cell membrane anchoring aptamer ligand. Acidic microenvironment-triggered the assembly of the TA-aptNC was characterized by electrophoresis and atomic force microscopic (AFM). The binding affinity and stability of the TA-aptNC, comparing the monovalent pH-aptDM, were studied via the flow cytometry and nuclease resistance assays. Acidic microenvironment-activated contrast-enhanced tumor imaging and significantly antitumor efficiency were evaluated in vitro and in vivo.Results: At physiological pH environment, the pH-aptDMs with excellent tissue permeability exited as inactivated and monodispersed small monomer. When encountering acidic microenvironment at the tumor site, pH-responsive i-motif switch liberated from the pH-aptDMs, and the three unconstrained DNA modules (DM1, DM2 and DM3) subsequently assembled in situ into the TA-aptNC. Compared with monovalent pH-aptDMs, the spontaneously formed activatable TA-aptNC afforded 2-fold enhanced binding ability via the multivalent effect, which further facilitated the selective tumor cell uptake capability, thus enabling a contrast-enhanced tumor imaging and significantly antitumor efficiency in vivo without systemic toxicity.Conclusions: The proposed strategy offers valuable insight into excavating an endogenous stimuli-triggered assembly of multivalent nanodevice for accurate diagnosis and efficient tumor therapy.

Light chain subunit of a poorly soluble human IgG2λ crystallizes in physiological pH environment both in cellulo and in vitro

Prominent inclusion bodies can develop in the endoplasmic reticulum (ER) when overexpressed antibodies possess intrinsically high condensation propensities. These observations suggest that antibodies deemed to show notable solubility problems may reveal such characteristics preemptively in the form of ER-associated inclusion bodies during antibody overexpression. To define the relationships between solubility problems and inclusion body phenotypes, we investigated the biosynthesis of a model human IgG2λ that shows severe opalescence in an acidic formulation buffer yet retains high solubility at physiological pH. Consistent with the pH-dependent solubility characteristics, the model antibody did not induce notable inclusion body in the physiological pH environment of the ER lumen. However, when individual subunit chains of the antibody were expressed separately, the light chain (LC) spontaneously induced notable crystal-like inclusion bodies in the ER. The LC crystallization event was readily reproducible in vitro by simply concentrating the purified LC protein at physiological pH. Two independent structural determinants for the LC crystallization were identified through rational mutagenesis approach by monitoring the effect of amino acid substitutions on intracellular LC crystallogenesis. The effect of mutations on crystallization was also recapitulated in vitro using purified LC proteins. Importantly, when introduced directly into the model antibody, a mutation that prevents the LC crystallization remediated the antibody's solubility problem without compromising the secretory output or antigen binding. These results illustrate that the ER can serve as a “physiological test tube” that not only reports secretory cargo's high condensation propensity at physiological pH, but also provides an orthogonal method that guides antibody engineering strategy.

Solid state and solubility study of a potential anticancer drug-drug molecular salt of diclofenac and metformin

To improve the physicochemical properties of diclofenac (DFA) and exert its potential anti-tumor effect in combined pharmacotherapy of metformin (MET), a new drug-drug molecular salt of DFA and MET (DFA-MET) is formed and characterized. The single-crystal X-ray diffraction analysis shows that DFA-MET is a three-dimensional (3D) supramolecular structure constructed by different hydrogen-bonding interactions between DFA and MET with 1:1 stoichiometry by proton transfer reaction. In addition, Hirshfeld Surface analysis shows that both the hydrogen-bonding interactions and the Vander Waals maintain the 3D supramolecular structure of DFA-MET together. Compared with pure DFA and pure diclofenac sodium (NaDFA), the dissolving behavior and permeability of DFA-MET by forming drug-drug molecular salt in physiological pH environments are enhanced remarkably.

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform.

Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms.

Stimuli-Responsive Polysaccharide Enveloped Liposome for Targeting and Penetrating Delivery of survivin-shRNA into Breast Tumor.

Silencing the inhibitor of apoptosis (IAP) by RNAi is a promising method for tumor therapy. One of the major challenges lies in how to sequentially overcome the system barriers in the course of the tumor targeting delivery, especially in the tumor accumulation and penetration. Herein we developed a novel stimuli-responsive polysaccharide enveloped liposome carrier, which was constructed by layer-by-layer depositing redox-sensitive amphiphilic chitosan (CS) and hyaluronic acid (HA) onto the liposome and then loading IAP inhibitor survivin-shRNA gene and permeation promoter hyaluronidase (HAase) sequentially. The as-prepared HA/HAase/CS/liposome/shRNA (HCLR) nanocarrier was verified to be stable in blood circulation due to the negative charged HA shield. The tumor targeting recognition and the enhanced tumor accumulation of HCLR were visualized by fluorescence resonance energy transfer (FRET) and in vivo fluorescence biodistribution. The deshielding of HA and the protonizing of CS in slightly acidic tumor extracellular pH environment (pHe, 6.8-6.5) were demonstrated by ζ potential change from -23.1 to 29.9 mV. The pHe-responsive HAase release was confirmed in the tumor extracellular mimicking environments, and the intratumoral biodistribution showed that the tumor penetration of HCLR was improved. The cell uptake of HCLR in pHe environment was significantly enhanced compared with that in physiological pH environment. The increased shRNA release of HCLR was approved in 10 mM glutathione (GSH) and tumor cells. Surprisingly, HCLR suppressed the tumor growth markedly through survivin silencing and meanwhile maintained low toxicity to mice. This study indicates that the novel polysaccharide enveloped HCLR is promising in clinical translation, thanks to the stimuli-triggered tumor accumulation, tumor penetration, cell uptake, and intracellular gene release.

A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function

Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-conductive gelatin. The as-synthesized PAMB-G copolymer is self-doped in physiological pH environments, making it an electrically active material in biological tissues. This copolymer is cross-linked by carbodiimide to form an injectable conductive hydrogel (PAMB-G hydrogel). The un-grafted gelatin hydrogel is prepared in a similar manner as a control. Both test hydrogels not only provide an optimal matrix for CM adhesion and growth but also maintain CM morphology and functional proteins. The conductivity of PAMB-G hydrogel is ca. 12 times higher than that of gelatin hydrogel. Microelectrode array analyses reveal that a heart placed on the PAMB-G hydrogel has a higher field potential amplitude than that placed on the gelatin hydrogel and can pass current from one heart to excite another heart at a distance. The injection of PAMB-G hydrogel into the scar zone following an MI in a rat heart improves electrical impulse propagation over that in a heart that has been treated with gelatin hydrogel, and synchronizes heart contraction, leading to preservation of the ventricular function and reduction of cardiac arrhythmia, demonstrating its potential for use in treating MI.

Development of photo-magnetic drug delivery system by facile-designed dual stimuli-responsive modified biopolymeric chitosan capped nano-vesicle to improve efficiency in the anesthetic effect and its biological investigations

Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency anesthetic drug delivery system. Chitosan is a unique class of biomaterials that is widely used in medical devices. The surface engineering of ZnFe2O4 nanoparticles was performed by coating with chitosan using simple precipitation method. Then, multi-active anesthetic drug (Lidocaine) was loaded into nano-ferrite to form a drug delivery vehicle. The prepared drug-vesicle was characterized by using XRD, FTIR, SEM, XPS and TGA analysis. XRD analysis proved the face center cubic structure of zinc nanoferrite. The sustained delivery of Lidocaine (LDC) from CS coated nanoferrite (CS/ZnFe2O4) was stimulated by pH and temperature responsive characteristics of vesicles. The in vitro cytotoxicity of the CS/ZnFe2O4 particles towards fibroblast cells was analyzed by using MTT assay. The drug loaded CS/ZnFe2O4 particles exhibit high biocompatibility and sustained drug release in the physiological pH environment (4.8, 5.5 and 7.4) and temperature responsive (25 and 37 °C) of normal tissues and also drug loading efficiency was measured.

Engineering a Remedy to Improve Phase Stability of Famotidine under Physiological pH Environments

Multicomponent crystals, essentially cocrystal engineering, comprise an emerging research area in pharmaceutical development which offer an easy solution to concerns with several drugs. Famotidine,...

Host–guest systems based on pH-sensitive acyclic cucurbit[n]urils for controlled release of camptothecin

Stimuli-responsive drug delivery systems may provide an effective way to treat cancer as they can release cargoes regularly according to changes in the human microenvironment. In this work, we design and prepare acid-controlled release complexes of camptothecin with three pH-sensitive acyclic cucurbit[n]urils. The inclusion complexes have been characterized by 1H and 2D nuclear magnetic resonance, X-ray powder diffraction, and phase solubility diagram. Cells incubated with complexes have been analyzed by high-content analysis, and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of CPT for clinical application.

Adaptable to Mechanically Stable Hydrogels Based on the Dynamic Covalent Cross-Linking of Thiol-Aldehyde Addition.

We exploit the thiol-aldehyde addition (TAA) reaction to build a dynamic covalent cross-linking (DCC) hydrogel in the physiological-pH environment. Due to the rapid and reversible TAA reaction, the resulting hydrogels are readily adapted for convenient manipulation, for example, free molding, easy injection, and self-healing. Meanwhile, the labile hemithioacetal bonds within the DCC hydrogel can convert to thermodynamically stable bonds via spontaneous thiol transfer reactions, thereby realizing poststabilization as needed. The successful application as a long-term scaffold for repair of barely self-healed bone defect indicated the hydrogels with both adaptability and mechanical stability based on thiol-aldehyde addition reaction is significant for biomedical areas.

Polymethyl methacrylate–ovalbumin @ graphene oxide drug carrier system for high anti-proliferative cancer drug delivery

High permeable drug delivery mechanism is indispensable for the treatment of various diseases including cancer. Protein-polymeric carriers have enhanced the permeability and therapeutic of bioactive compounds. Here, polymethyl methacrylate (PMMA) as polymer and egg white protein of ovalbumin (OVA) from a natural source of quail egg was developed for the highly permeable biocompatible drug delivery system. A significant anti-cancer drug doxorubicin (DOX) was loaded on this drug delivery system. Graphene oxide (GO)-functionalized OVA–PMMA drug delivery system has increased the surface for an accumulation of drug. The drug-loading capacity and controlled release of the drug were investigated through the dialysis technique with various physiological pH environments. The effect of DOX and GO on the morphology of OVA–PMMA matrix was studied with the help of FT-IR and XRD patterns. Dynamic light scattering study gives the data about the particle size of this OVA–PMMA–GO and OVA–PMMA–GO–DOX. These data matched with the image obtained from SEM and TEM instruments. Cytotoxicity effect and cellular uptaking of DOX-loaded OVA–PMMA and OVA–PMMA–GO were investigated on gastric cancer cell line and normal cell line. All these characterizations of this study reveal that the drug is successfully loaded on this new drug carrier and controlled release was achieved.

Acid-controlled release complexes of podophyllotoxin and etoposide with acyclic cucurbit[n]urils for low cytotoxicity.

The targeted or responsive systems are appealing therapeutic platforms for the development of next-generation precision medications. So, we design and prepare acid-controlled release complexes of podophyllotoxin (POD) and etoposide (VP-16) with pH-labile acyclic cucurbit[n]urils, and their characteristics and inclusion complexation behaviors were investigated via fluorescence spectroscopy, nuclear magnetic resonance and X-ray power diffraction. Cells incubated with complexes have been analyzed by high-content analysis (HCA), and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of POD and VP-16 for clinical application.

Influence of dendrimer surface chemistry and pH on the binding and release pattern of chalcone studied by molecular dynamics simulations.

Poly(amidoamine) (PAMAM) dendrimers are promising nanocarriers that can enhance the solubility of hydrophobic drugs. The surface chemistry of dendrimers is of great relevance as end groups of these nanocarriers can be easily modified to improve the bioavailability and sustained release of the cargo. Therefore, a molecular-level understanding of the host-guest interactions that can give both qualitative and quantitative information is particularly desirable. In this work, fully atomistic molecular dynamics simulations were used to study the association of a bioactive natural product, ie, chalcone, with amine-, acetyl-, and carboxyl-terminated PAMAM dendrimers at physiological and acidic pH environments. Amine- and carboxyl-terminated PAMAM dendrimers have an open microstructure at low pH that is not able to hold the ligand tightly, resulting in an unfavorable encapsulation of the chalcone molecule. In the case of acetyl-terminated dendrimer, chalcone molecule diffuses out of the dendritic cavities a few times during the simulation time and prefers to locate close to the surface of dendrimer. Average center of mass distance values at neutral pH showed that the chalcone molecule bounds firmly in the internal pockets of amine-, acetyl-, and carboxyl-terminated dendrimers and forms stable complexes with these nanovectors. The potential of mean force calculations showed that the release of the ligand from the dendrimers occurs at a controlled rate in the body.

Mechanical characteristics of biodegradable magnesium matrix composites: A review

Abstract In recent years, a new generation of biodegradable metallic materials, magnesium alloys, has been called a revolutionary material for biomedical applications ( i.e. in orthopedics applications as a bone-implant material), thanks to the reasonable strength (similar to bone tissue, compared to available metallic alloys) and high biocompatibility of magnesium and its alloys. However, pure magnesium can corrode too quickly in the physiological pH (7.4–7.6) and high chloride environment of the physiological system and therefore lose their mechanical integrity before tissues have sufficiently. Engineering approach to this challenge (high corrosion rate of Mg) can be ( i ) alloying of element additions, ( ii ) surface treatment and ( iii ) development of metal (magnesium) matrix composites (MMCs). Magnesium-based composites, as bio-materials, can provide a combination of unique characteristics including adjustable mechanical properties ( i.e. tensile strength, elastic modulus, ductility) and corrosion resistance. This is the main advantage of magnesium-based composites as compared with alloying and surface treatment approaches. Here, the matrix materials are biomedical magnesium alloys based on Mg–Zn, Mg–Ca and Mg–REE alloy systems (REE stands for rare earth elements including yttrium, Y, cerium, Ce, lanthanum, La). The reinforcement phases are mainly based on hydroxyapatite (HAP), calcium polyphosphate (CPP), and β-tricalcium phosphate (β-TCP) particles, and hybrid HAP + β-TCP particles. In this paper a comprehensive review is provided on different grades of biodegradable magnesium matrix composites, with focus on their mechanical properties.